We plan to assess several areas of importance to the field of alcoholism and its effects. 1) Sedatives in Health and Liver Disease. We will assess the effects of alcohol acutely and after its chronic administration on the hepatic metabolism of various benzodiazepine sedatives. The acute studies will be carried out with rat liver microsomes exposed in vitro to varying alcohol concentrations as well as to alcohol degradation products, acetaldehyde and acetate. The effects of these on the microsomal enzymatic machinery will be determined. In the chronic studies drug metabolism will be measured in vivo first and then with liver of such animals prepared for in vitro study. Other studies will be directed at assessing the effects of alcoholic liver disease on morphine elimination in vivo. Other investigations on sedatives will evaluate the sensitivity of the brain in the aged, patients with alcoholic liver disease, those smoking and those who are alcoholics without liver disease to various benzodiazepines. This assessment of drug pharmacodynamics will utilize computerized psychometric performance and EEG analysis. 2) Thiamine Metabolism. We will continue our studies on intestinal thiamine transport by assessing a) thiamine uptake by human intestine normally and following alcohol, b) the effect of other water soluble vitamin deficiencies on thiamine transport by rat gut, and c) the importance of phosphorylation for normal active thiamine transport. The former will consist of the triple lumen technique and the latter will utilize both in vivo gut loops and in vitro gut sacs and radiolabelled thiamine. The individual thiamine moieties will be separated by high pressure liquid chromatography and their time course of gut uptake with and without various inhibitors will be measured. 3) Fetal-Alcohol Syndrome. We plan to continue our studies on the transport of amino acids via the rat placenta obtained from animals exposed to alcohol for varying periods of time.